An effective innovative pedagogy for sexual health education is required to meet the demands of technology savvy digital natives. This study investigates the extent to which game-based learning (GBL) and gamification could improve the sexual health education of adolescent students. We conducted a randomized control trial of GBL and gamification experimental conditions. We made a comparison with traditional teaching as a control condition in order to establish differences between the three teaching conditions. The sexual health education topics were delivered in a masked fashion, 40-min a week for five weeks. A mixed-method research approach was uses to assess and analyze the results for 120 students from a secondary school in Dar Es Salaam, Tanzania. Students were divided into groups of 40 for each of the three teaching methods: GBL, gamification, and the control group (the traditional teaching method). The average post-test scores for GBL (Mean = 79.94, SD = 11.169) and gamification (Mean = 79.23, SD = 9.186) were significantly higher than the control group Mean = 51.93, SD = 18.705 (F (2, 117) = 54.75, p = 0.001). Overall, statistically significant differences (p ≤ 0.05) were found for the constructs of Motivation, Attitude, Knowledge, and Engagement (MAKE). This study suggests that the two innovative teaching approaches can be used to improve the sexual health education of adolescent students. The methods can potentially contribute socially, particularly in improving sexual health behaviour and adolescents’ knowledge in regions plagued by years of sexual health problems, including HIV/AIDS